A Study to Evaluate the Pharmacokinetics (PK), Safety and Tolerability of TAK-788 Followed by Evaluation of the Effects of a Low-Fat Meal on TAK-788 PK and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Participants

Healthy Volunteers Clinical Trial

Official title:

Phase 1, Randomized, Double-blind, Placebo-Controlled, Single Rising Dose Study to Evaluate Pharmacokinetics, Safety, and Tolerability of TAK-788 Followed by Open-Label, Crossover Evaluation of the Effects of a Low-Fat Meal on TAK-788 Pharmacokinetics and Evaluation of Relative Bioavailability of TAK-788 Capsules in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03482453
• Other study ID #: TAK-788-1001
• Secondary ID: U1111-1208-9582
• Status: Completed
• Phase: Phase 1
• Start date: March 28, 2018
• Est. completion date: January 18, 2019

Study information

• Verified date: January 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability of TAK-788 and to identify a tolerable single oral dose of TAK-788 administered as a drug-in-capsule (DiC) formulation, to characterize the effects of a low-fat meal on the PK of the TAK-788 administered as DiC formulation and to evaluate the bioavailability of a test (Process B) DiC of TAK-788 relative to a reference (Process A) DiC of TAK-788 in healthy participants.

Description:

The drug being tested in this study is called TAK-788. The study will assess the safety and tolerability of single oral dose of TAK-788, evaluate the effect of a low-fat meal on PK of TAK-788 and will assess the relative bioavailability of two DiCs of TAK-788.

The study will enroll approximately 69 participants. The study is designed to consist of 3 parts: Part 1- dose escalation phase, Part 2- low fat meal effect and Part 3 - relative bioavailability. The study population of Part 1 will consist of 40 participants enrolled into 5 cohorts. Each cohort will have 8 randomized participants with 6 receiving a single dose of TAK-788, and 2 receiving matching placebo under fasted conditions. In Cohorts 1 to 5, safety of single-dose TAK-788 will be evaluated. For Part 2, the effect of a low-fat meal on a single tolerable dose of TAK-788 will be determined following review of safety and tolerability data from the previous cohorts in Part 1. The study population of Part 2 will consist of 16 participants enrolled into 2 cohorts of different doses, where participants will be randomized to a cross-over sequence of:

• TAK-788 Fed + TAK-788 Fasted

• TAK-788 Fasted + TAK-788 Fed

The study population of Part 3 will consist of 13 participants enrolled into 1 cohort, where participants will be randomized to a cross-over sequence of:

• TAK-788 DiC (reference) + TAK-788 DiC (test)

• TAK-788 DiC (test) + TAK-788 DiC (reference) This single-center trial will be conducted in the United States. The overall time to participate in this study is approximately 7 months. Participants will be contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: January 18, 2019
• Est. primary completion date: December 22, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Body weight of greater than or equal to (>=) 45 kilogram (kg) (women) or >=55 kg (men) and a body mass index of 18.0 to 30.0 kilogram per square meter (kg/m^2) at screening.

2. Nonsmoker (never smoked or greater than [>] 20 years from last occurrence of smoking).

3. Normal organ function including hepatic, renal, and bone marrow function.

Exclusion Criteria:

1. Manifestations of malabsorption due to prior gastro-intestinal (GI) surgery, GI disease, or for an unknown other reason that may alter the PK of TAK-788.

2. Pulmonary infection ongoing or within 30 days of informed consent.

3. Inability to undergo venipuncture and/or tolerate venous access.

4. Inability to tolerate multiple blood sampling.

5. Ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• TAK-788
TAK-788 capsules.
• Placebo
TAK-788 placebo-matching capsules.
• TAK-788
TAK-788 DiC.

Locations

Country	Name	City	State
United States	PRA Health Sciences	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)		Baseline up to 30 days after the last dose of study drug (Day 31)
Primary	Part 1: Number of Participants With One or More Serious Adverse Events (SAEs)		Baseline up to 30 days after the last dose of study drug (Day 31)
Primary	Part 1: Number of Participants With Clinically Significant Abnormal Laboratory Values		Baseline up to 30 days after the last dose of study drug (Day 31)
Primary	Part 1: Number of Participants With Clinically Significant Abnormal Vital Signs		Baseline up to 30 days after the last dose of study drug (Day 31)
Primary	Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-788		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Primary	Part 3, Cmax: Maximum Observed Plasma Concentration for TAK-788		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Primary	Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Part 2, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Primary	Part 3, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Part 2, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Primary	Part 3, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Primary	Part 2, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Primary	Part 3, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788		Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose
Secondary	Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-788 and Its Active Metabolites AP32960 and AP32914		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary	Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-788 and Its Active Metabolites AP32960 and AP32914		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary	Part 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for TAK-788 and Its Active Metabolites, AP32960 and AP32914		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary	Part 1, AUC8: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-788 and Its Active Metabolites AP32960 and AP32914		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary	Part 1, t1/2z: Terminal Disposition Phase Half-life (t1/2z) for TAK-788 and Its Active Metabolites AP32960 and AP32914		Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary	Parts 2 and 3: Number of Participants Reporting One or More TEAEs		Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Secondary	Parts 2 and 3: Number of Participants With One or More SAEs		Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Secondary	Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Laboratory Values		Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)
Secondary	Parts 2 and 3: Number of Participants With Clinically Significant Abnormal Vital Signs		Baseline up to 30 days after the last dose of study drug (Day 38) (end of Intervention Period 2)